"Dear Steve, I saw a patient this morning with your book [in hand] and highlights throughout. She loves it and finds it very useful to help her in dealing with atrial fibrillation."

Dr. Wilber Su,Cavanaugh Heart Center, Phoenix, AZ

"...masterful. You managed to combine an encyclopedic compilation of information with the simplicity of presentation that enhances the delivery of the information to the reader. This is not an easy thing to do, but you have been very, very successful at it."

Ira David Levin, heart patient, Rome, Italy

"Within the pages of Beat Your A-Fib, Dr. Steve Ryan, PhD, provides a comprehensive guide for persons seeking to find a cure for their Atrial Fibrillation."

Stem Cells

9. “I’ve read about stem cells research to regenerate damaged heart tissue. Could this help cure A-Fib patients?”

Yes, this fascinating research, though not directed specifically to Atrial Fibrillation, may prove to be very important to A-Fib patients. These groundbreaking studies focus on using stem cells to regenerate damaged heart tissue.

Working with heart attack victims who had suffered major heart scarring, doctors infused into their damaged hearts, stem cells that had been harvested and grown from their own heart.

The results were astounding!

Scar tissue decreased—shrinking between 30% to 47%. New heart tissue was generated—the stem cell recipients grew the equivalent of 600 million new heart cells. Their ejection fraction increased from the low 30% range to almost normal. Patients who received these stem cells had significant improvements in heart function, physical capacity, and scored better on quality-of-life questionnaires. MRI and ultrasound imaging revealed that areas where stem cells were infused showed major improvement which continued for over a year.

Their heart damage was reversed without dangerous side effects.

What does this mean to A-Fib patients? For someone with Atrial Fibrillation, the research studies’ terms of ‘scar tissue’ and ‘heart damage’ translates to ‘fibrosis’, that is, tissue that becomes fibrous and inflexible. Fibrosis in A-Fib patients is linked to enlargement of the heart and the increased threat of stroke.

if injected stem cells can somehow signal the heart to repair itself, this may turn the A-Fib patient’s fibrosis and scarring back into normal heart muscle. The fibrosis and scarring associated with A-Fib would no longer be permanent and irreversible.

Maybe someday we could be cured of A-Fib through stem cell infusion rather than with ablation burns or surgery.

FAQs: Understanding Atrial Fibrillation

Atrial Fibrillation patients often have loads of “Why?” and “How?” questions. Here are answers to the most frequently asked questions by patients and their families. (Click on the question to jump to the answer.)

Related Question: “My cardiologist recommends a pacemaker. I have paroxysmal A-Fib with “pauses” at the end of an event. Will they stop if my A-Fib is cured? I am willing, but want to learn more about these pauses first.”

In a remarkable experimental study using mice hearts, Israeli scientists discovered that the Left Atrial Appendage is a reservoir of different types of stem cells which can stimulate the heart to repair itself.

This study confirms the revolutionary view that the heart contains stem cells which help heal diseased tissue. These stem cells function as progenitor cells, that is, they can regenerate and turn into not only cardiac muscle cells, but also other kinds of cells such as blood vessels, connective tissue, and, “most importantly, a certain kind of cardiac tissue that is important for the body’s immune system.”

In other words, cells from the Left Atrial Appendage have“the ability to stimulate an injured heart to heal itself.”

Though groundbreaking, this research is preliminary. Further experimental studies are necessary to determine how exactly and under what conditions these LAA stem cells work. Are they vestigial or a remnant reservoir of stem cell building blocks left over from fetal and early childhood development and which now serve no or little active function? The study did not imply there was an actual ongoing repair mechanism in the heart from these progenitor cells in the LAA. And is the LAA the only source of cardiac repair? Many people over the years have had their LAAs removed or closed off without seemingly dire consequences to their heart health. (Thanks to Pete for calling our attention to this article and its importance.)

The Left Atrial Appendage (LAA) Defined

The Left Atrial Appendage (LAA) is a pocket or sleeve-like structure on the outside top of the left atrium which opens into the left atrium. It’s a complicated structure with often more than one lobe. From an embryonic perspective, the LAA is more related to the ventricles than to the smooth-walled atrium. It has a distinct anatomy which contains numerous trabeculae (muscle fibers) which resemble the ventricles.

In the first trimester or two of our time in the womb, the Left Atrial Appendage (LAA) was originally our left atrium (LA). When the final real Left Atrium (LA) formed gradually from the conjunction and evolutionary development of the four pulmonary veins, the actual LA chamber grew and ballooned out, pushing the smaller remnant LA up to the left top of the Left Atrium where it became known as the Left Atrial Appendage (LAA) with its own functions and behaviors. But as we age and as heart disease/A-Fib, etc. start to set in, the LAA can turn into “the most lethal, no longer essential appendage in the human anatomy.” (Thanks to Shannon Dickson for these insights about the LAA.)

Most A-Fib blood clots which cause stroke come from the Left Atrial Appendage. By closing off the Left Atrial Appendage, most but not all risk of stroke is eliminated even if you are still in A-Fib.

Functions of the Left Atrial Appendage

The Left Atrial Appendage functions like a reservoir or decompression chamber or a surge tank on a hot water heater to prevent surges of blood in the left atrium when the mitral valve is closed.Without it, there is increased pressure on the pulmonary veins and left atrium which might possibly lead to heart problems later.

Cutting out, stapling shut or closing off the LAA reduces the amount of blood pumped by the heart and may result in exercise intolerance for people with an active life style. (In dogs the LAA provides 17.2% volume of blood pumped by the Left Atrium.)

The LAA also has a high concentration of Atrial Natriuretic Factor (ANF) granules which help to reduce blood pressure. The LAA functions as a storage device for ANF. But recent preliminary research indicates that the Right Atrial Appendage compensates for the loss of the LAA by producing more ANF.

The Left Atrial Appendage may also function as a reservoir of different types of stem cells which can stimulate the heart to repair itself (thanks to the research of the above Israeli scientists).

Should the Left Atrial Appendage be Routinely Cut Out or Closed Off?

Almost all surgical treatments for A-Fib cut out or close off the Left Atrial Appendage (LAA). In A-Fib, blood stagnates in the LAA and clots tend to form. The rationale for closing off the LAA is that, in case the surgery fails which happens occasionally, the patient is still protected from having an A-Fib stroke. 90%-95% of A-Fib strokes come from clots which originate in the LAA. By closing off the Left Atrial Appendage, most but not all risk of stroke is eliminated even if you are still in A-Fib.

And even if a person is no longer in A-Fib, closing off the LAA may still prevent a stroke. The LAA is where most clots originate. If a surgeon is already working on the heart, why not close off the LAA and reduce the patient’s chance of having a future stroke? (If a surgeon doesn’t close off the LAA, they could be sued if a patient later had a stroke, even if the patient was no longer in A-Fib.) Living with a greatly reduced risk of stroke is more important for most people even at the loss of the functions of the LAA.

In the future even people without A-Fib may have their Left Atrial Appendage closed off if it prevents or reduces the risk of a stroke. This may be more important for older people, particularly women, who are at a greater risk of stroke as we age. There are currently a variety of devices, surgical and non-surgical, which can do this. (LAA closure may be an important new way to reduce strokes, particularly in the elderly.)

Why are we more at risk of a stroke as we age? Abnormal platelet aggregation (clumping, platelets sticking together) tends to increase as we age. Any blood particle larger than 5-10 micrometers can clog capillaries. Capillaries are tiny and very narrow—with a diameter of only 8-10 micrometers on average, while platelets are usually 2-4 micrometers. If they clump together, it doesn’t take much to block a capillary. If enough capillaries become blocked in the brain, an ischemic stroke can occur. Older people tend to be less active and have weaker hearts which can result in less blood flow or perfusion (hypoperfusion) and more platelet clumping. (This lower perfusion in the brain also produces cognitive decline over time.)

No Option if You Want to have Surgery for A-Fib?

For patients undergoing A-Fib surgery in the US, surgeons automatically remove/close off your LAA. Patients aren’t offered the option of not having the LAA removed. It’s not the same in other countries where removing the LAA isn’t automatic. What triggers the removal? The LAA isn’t removed unless a patient has “a CHADS2 score ≥1, in the presence of rapid firing coming from the left atrial appendage (LAA), and when the procedure is deemed safe

But some question the need or benefit of removing the LAA if one is no longer in A-Fib after surgery. For a patient made A-Fib free, would their heart function better or more normally if they still had their LAA? Few clinical studies have been done on this subject. The author isn’t aware of any Surgeons (or EPs) who do pre- and post-LAA closure measurements of exercise ability, heart pumping function, etc. of the heart with and without the Left Atrial Appendage.

Conclusions

Close off the Left Atrial Appendage? Though this is a hard call, I’d recommend holding on to your Left Atrial Appendage (LAA) as long as possible. In addition to the first three functions of the LAA described above, this new Israeli study demonstrates that the LAA functions as a reservoir of different types of stem cells which can stimulate the heart to repair itself. This may turn out to be an invaluable, irreplaceable function of the LAA more important for heart health than all the others.

But as we age and/or develop A-Fib, we may have to have our LAA removed or closed off to prevent a stroke which can be a fate worse than death. This is a decision to be made with your doctor and may change as you age and change.

Dr. M (John Mandrola) in his excellent blog described fascinating research using stem cells to regenerate damaged heart tissue.

Patients who had suffered a heart attack or who had advanced heart failure and heart muscle damage received infusions of stem cells grown from cells taken from a biopsy of their own heart.

Heart Stem Cells Harvested, Purified Then Grow

Dr. Robert Bolli of the University of Louisville and Dr. Piero Anversa at Brigham and Women’s Hospital/Harvard Medical School took the heart stem cells harvested from patients during coronary artery bypass surgery and sent them to Boston where they were purified and allowed to grow.

Cells Infused Back into The Patient’s Heart

Once there were about 1 million of the stem cells per patient, Dr. Bolli’s team in Louisville reintroduce them into the region of the patient’s heart that had been scarred by a heart attack. The purified batch of cardiac stem cells was infused into the patients’ hearts approximately 4 months after their bypass surgery, allowing time for the bypass surgery to heal.

Amazing Results: Heart Damage Reversed!

The results were beyond their wildest expectations. Ejection fraction increased and the amount of scarring and damaged cells decreased. Heart damage was reversed without dangerous side effects. At the start of the study Dr. Bolli’s patients had an average ejection fraction of 30.3%. Four months after receiving stem cells, their ejection fraction was 38.5%. Some patients followed for a full year improved to an an astounding 42.5%.A control group given nothing but standard maintenance medications showed no improvement at all.

Similar Research Studies

Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute, developed a similar stem cell procedure. He found that not only did scar tissue decrease—shrinking between 30% and 47% in patients—but the patients actually generated new heart tissue. On average, the stem cell recipients grew the equivalent of 600 million new heart cells, according to Dr. Marban, who used MRI imaging to measure changes. (A major heart attack might kill off 1 billion heart cells.)

Dr. Anversa found that the heart contains a type of stem cell that can develop into either heart muscle or blood vessel components—whatever the heart needs depending on its injury. But there usually aren’t enough of these heart stem cells available after a heart attack. To provide a patient more of these heart stem cells, the doctors removed heart stem cells by a biopsy and then made millions of copies in a laboratory.

Different Strategies

Drs. Bolli and Anversa and Dr. Marban both used cardiac stem cells, but Drs. Bolli and Anversa “purified” the cardiac stem cells so that more than 90% of the infusion was actual stem cells. Dr. Marban, on the other hand, used a mixture of stem cells and other types of cells extracted from the patient’s heart. “We found that the mixture is more potent than any subtype we’ve been able to isolate,” he says.

The additional cells may help by providing a supportive environment for the stem cells to multiply. Other scientists have produced improvements in cardiac patients using stem cells derived from bone marrow, though the results aren’t as spectacular as the above studies.

Dr. Bolli’s study (called “SCIPIO’) was the first reported human study of heart derived stem cells. Patients who received these stem cells had significant improvements in heart function, physical capacity and scored better on quality-of-life questionnaires. MRI and ultrasound imaging revealed that areas where stem cells were infused showed major improvement which continued over a year.

Editor’s Comments:
Though this study was not directed to A-Fib patients, let’s fantasize a bit. This study shows that heart stem cells can replace scar tissue and fibrosis with normal beating heart muscle fibers, thereby restoring heart function. Fibrosis and scarring, which are normally considered irreversible heart damage, may no longer be permanent.

Though the jury is still out on this, some studies indicate that fibrosis is associated with A-Fib. (see 2013 BAFS: A-Fib Produces Fibrosis—Experimental and Real-World Data). And fibrosis is linked to the threat of an A-Fib stroke (see BAFS 2014:High Fibrosis at Greater Risk of Stroke and Precludes Catheter Ablation: Lessons Learned from the DECAAF Trial). if injected stem cells somehow signal the heart to repair itself, this may turn fibrosis and scarring back into normal heart muscle.

In the near future a patient with A-Fib, instead of having to undergo catheter ablation (or surgery), may instead receive an injection of their own heart stem cells and be cured of A-Fib and the threat of an A-Fib stroke.

The only risk would be getting a biopsy inside the heart to get a sampling of heart tissue stem cells, then months later another procedure to insert the purified and multiplied heart stem cells. Though not simple procedures, they would probably involve less or at least an equal amount of risk as a catheter ablation but with no permanent scarring through ablation.

(This strategy probably couldn’t be used in someone who has already had a catheter ablation [or surgery]. The heart stem cells might heal the scarring created by the ablation, thereby causing reconnection or regrowth. Though it’s unlikely that stem cells would heal the structural scarring of ablation burns.)

Right now the costs of standard (non-heart) stem cell injection is around $4,000-$5,000 per injection. But currently very few doctors around the US do it.

Prediction:
The author predicts that heart stem cells injection will rapidly become a standard treatment option, even for A-Fib patients. There shouldn’t be any political or religious objections to this heart stem cell therapy, since it doesn’t rely on embryonic stem cells.

Cardiac stem cell injection is probably a major medical breakthrough for A-Fib patients. Heart stem cell injection regenerates heart muscle. In Dr. Bolli’s words, “if a phase 3 study confirm this, it would be the biggest advance in cardiology in my lifetime. We would possibly be curing heart failure. It would be a revolution.” And this revolution will probably work in patients with A-Fib.

Disclaimer: the authors of this Web site are not medical doctors and are not affiliated with any medical school or organization. The information on this site is not intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health professional prior to starting any new treatment or with any questions you may have regarding a medical condition. Nothing contained in this service is intended to be for medical diagnosis or treatment.